Epigenetic mechanisms of epithelial - immune interactions that shape immune surveillance in the intestinal epithelium

Garipcan, Aybuke, Eskiocak, Onur, Subhash, Santhilal, Ozler, Kadir, Yueh, Brian, Chung, Charlie, Ergin, Ilgin, Gautier, Nelson, Habel, Jill, Rubino, Rachel, Van der Velden, Adrianus WM, Beyaz, Semir (2023) Epigenetic mechanisms of epithelial - immune interactions that shape immune surveillance in the intestinal epithelium. In: UNSPECIFIED.

Abstract

Immune surveillance of the intestinal epithelium is regulated by the reciprocal interactions between intestinal epithelial cells, immune system and microbiome. This highly specialized compartment maintains the tolerance against dietary products and commensal bacteria while protecting the epithelium against pathogens, cancer risk and tissue damage. While recent studies identified epigenetic mechanisms that orchestrate the self-renewal and differentiation of intestinal epithelial cells (IECs), little is known about the mechanisms that govern epithelial – immune interactions and how they influence immune surveillance and tissue regeneration. Here we dissect epithelial-intrinsic epigenetic features including transcription factors and co-activators that govern immune surveillance of intestinal epithelium using genetically engineered mouse models and autologous human patient-derived organoid – immune co-cultures. Ablation of epigenetic regulators that associate with immune interaction gene modules specifically in IECs dampens intraepithelial lymphocyte-mediated immune surveillance. We identified precise epigenetic mechanisms of epithelial – immune interactions including promoter and enhancer regulation by transcription factors and co-activators both in mice and humans. Finally, disruption of the epigenetic regulators that maintain epithelial – immune interactions lead to impaired responses in clinically-relevant mouse models of infection, tissue regeneration and cancer. These results establish a strong foundation towards understanding the epigenetic mechanisms that govern multi-cellular interactions within the barrier tissues in physiology or disease states.

Item Type:	Conference or Workshop Item (Paper)
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell organs, tissues, organelles, cell types and functions
CSHL Authors:	Garipcan, Aybuke Eskiocak, Onur Subhash, Santhilal Ozler, Kadir Yueh, Brian Chung, Charlie Habel, Jill Rubino, Rachel Beyaz, Semir
Communities:	CSHL labs > Beyaz lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2023
Date Deposited:	16 Jan 2024 14:11
Last Modified:	16 Jan 2024 14:11
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41397

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